Intestinal Transglutaminase Antibodies in Celiac Disease Diagnosis

Use of Intestinal Transglutaminase Antibodies in the Diagnosis of Celiac Disease in Children and Adults: a Multicenter Prospective Study

Celiac disease (CD) is a systemic autoimmune gluten-dependent enteropathy in subjects with HLA DQ2/8. CD prevalence is more than 1% with a progression to 2% in adulthood. Among the group at risk such as first-degree relatives, subjects with autoimmune diseases (eg type 1 diabetes) or with syndromes (Down's disease, Turner) the prevalence reaches 5-8%. Recently, in pediatrics CD diagnostic criteria have been modified and the intestinal biopsy can be omitted in presence of a specific clinical and laboratory picture. In the remaining pediatric cases and in all adult patients, the biopsy is fundamental for the diagnosis. The clinical manifestation of CD not always depends on the enteropathy and on the related symptoms, but it can be characterized by extra-intestinal symptoms (eg chronic fatigue, anemia, arthralgia, cerebellar ataxia, alterations of dental enamel) that often hamper a rapid CD recognition delaying the diagnosis especially in adults. Symptoms are not always related to intestinal injury and may be present even when intestinal mucosa is normal. This condition is known as potential CD in which serum IgA anti-transglutaminase antibodies (anti-ttg) are generally positive at low concentrations (eg higher 2-3 times than the cut-off) or positive occasionally. In this clinical context, the gluten-free diet is an effective therapy able to improve the clinical picture and to stop the anti-ttg production. Recent observations, especially in pediatric field, have shown that in potential CD the immunological analysis of intestinal biopsies is characterized by the presence of anti-ttg deposits in the intestinal mucosa which predict the development of intestinal atrophy in a time span of 3- 5 years. Furthermore, these deposits disappear with the diet-therapy. In pediatric field, the diagnostic specificity of mucosal anti-ttg (anti-ttg-m) is between 95-98%, while the sensitivity is 100%. In adults, anti-ttg-m show 100% sensitivity in typical celiac disease (characterized by high serum anti-ttg concentrations and intestinal mucosa atrophy), while no results are available about potential celiac disease. Moreover, in adults data about the specificity of anti-ttg-m in infectious, oncological and inflammatory diseases of the gastro-intestinal tract are not available. The main study objectives are to evaluate anti-ttg-m sensitivity in patients with typical celiac disease and anti-ttg-m specificity in patients with oncological and inflammatory bowel diseases.

Inclusion Criteria:

• Pediatric and adult subjects
• Subjects with clinical suspicion of CD, positive serum anti-ttg concentrations with any value or type of presentation (permanent or fluctuating)
• Asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD (eg family members of CD patients, subjects with autoimmune diseases)
• Subjects undergoing gastro-intestinal endoscopy for infectious (eg Helicobacter pylori gastritis), oncologic (tumors of the gastro intestinal tract) or inflammatory disorders (Crohn disease, ulcerative colitis, eosinophilic esophagitis) in acute phase or in remission

Exclusion Criteria:

• Subjects in whom to take biopsies is not indicated during the gastro-intestinal endoscopy
• Subjects with oncological pathology undergoing chemotherapy treatment because anti-blastic agents may play an inhibitory activity in the production of immunoglobulins